A Review of the Effects of Particulate Matter Air Pollution on Human Health

REVIEW ARTICLEClearing the Air:A Review of the Effects of Particulate Matter Air Pollution on Human HealthJonathan O.Anderson &Josef G.Thundiyil &Andrew StolbachPublished online:23December 2011#American College of Medical Toxicology 2011Abstract The World Health Organization estimates that par-ticulate matter (PM)air pollution contributes to approximately 800,000premature deaths each year,ranking it the 13th leading cause of mortality worldwide.However,many studies show that the relationship is deeper and far more complicated than origi-nally thought.PM is a portion of air pollution that is made up of extremely small particles and liquid droplets containing acids,organic chemicals,metals,and soil or dust particles.PM is categorized by size and continues to be the fraction of air pollution that is most reliably associated with human disease.PM is thought to contribute to cardiovascular and cerebrovas-cular disease by the mechanisms of systemic inflammation,direct and indirect coagulation activation,and direct transloca-tion into systemic circulation.The data demonstrating PM's effect on the cardiovascular system are strong.Populations subjected to long-term exposure to PM have a significantly higher cardiovascular incident and mortality rate.Short-term acute exposures subtly increase the rate of cardiovascular events within days of a pollution spike.The data are not as strong for PM's effects on cerebrovascular disease,though some data and similar mechanisms suggest a lesser result with smaller ampli-tude.Respiratory diseases are also exacerbated by exposure to PM.PM causes respiratory morbidity and mortality by creating oxidative stress and inflammation that leads to pulmonary ana-tomic and physiologic remodeling.The literature shows PMcauses worsening respiratory symptoms,more frequent medica-tion use,decreased lung function,recurrent health care utiliza-tion,and increased mortality.PM exposure has been shown to have a small but significant adverse effect on cardiovascular,respiratory,and to a lesser extent,cerebrovascular disease.These consistent results are shown by multiple studies with varying populations,protocols,and regions.The data demonstrate a dose-dependent relationship between PM and human disease,and that removal from a PM-rich environment decreases the prevalence of these diseases.While further study is needed to elucidate the effects of composition,chemistry,and the PM effect on susceptible populations,the preponderance of data shows that PM exposure causes a small but significant increase in human morbidity and mortality.Most sources agree on certain “common sense ”recommendations,although there are lonely limited data to support them.Indoor PM exposure can be reduced by the usage of air conditioning and particulate filters,decreasing indoor combustion for heating and cooking,and smoking cessation.Susceptible populations,such as the elderly or asthmatics,may benefit from limiting their outdoor activity during peak traffic periods or poor air quality days.These simple changes may benefit individual patients in both short-term symptomatic control and long-term cardiovascular and respira-tory complications.Keywords Particulate matter .Air pollution .Cardiovascular .Respiratory .Public policyIntroductionWhile some correlation between poor air quality and human disease has been recognized since antiquity,the health effects of air pollution entered the world's consciousness in the twentieth century.In 1930,sulfur dioxide from localJ.O.Anderson (*):J.G.Thundiyil Department of Medical Education,Orlando Health Emergency Medicine,86W.Underwood.Suite 200,Orlando,FL 32806,USAe-mail:janders120@A.StolbachJohns Hopkins University Emergency Medicine,1830E.Monument St.Suite 6-100,Baltimore,MD 21287,USAJ.Med.Toxicol.(2012)8:166–175DOI 10.1007/s13181-011-0203-1factory emissions mixed with a dense fog over the Meuse Valley in Belgium.Over3days,several thousand people were stricken with acute pulmonary symptoms,and60 people died of respiratory causes[1].In December1952,a dense smog containing sulfur dioxide and smoke particulate descended upon London,resulting in more than3,000ex-cess deaths over3weeks and as many as12,000through February1953[2].The lethality of air pollution was imme-diately recognized but not well understood.To this day, because the effects of air pollution on illness occur at a population level,many clinicians fail to appreciate the rela-tionship between air pollution and health.The1970Clean Air Act(CAA)was the first major Amer-ican regulatory effort aimed at both studying and setting limits on emissions and air pollution.The1970CAA defined the National Ambient Air Quality Standards(NAAQS[3]).These standards set limits on six primary pollutants found in air: carbon monoxide,lead,nitrogen dioxide,ozone,sulfur diox-ide,and particulate matter(PM)[4].PM is a complex mixture of extremely small particles andliquid droplets made up of acids,organic chemicals,metals, and soil or dust particles[5].Sources of PM are both natural and anthropogenic.Manmade sources of PM include com-bustion in mechanical and industrial processes,vehicle emissions,and tobacco smoke.Natural sources include vol-canoes,fires,dust storms,and aerosolized sea salt.PM can be described by its“aerodynamic equivalent diameter”(AED).Particles of the same AED will tend to have the same settling velocity.Researchers traditionally subdivide particles into AED fractions based on how the particles are generated and where they deposit in human airways:<10,<2.5,and<0.1μm(PM10,PM2.5,and PM0.1, respectively).Particles with a diameter greater than10μm have a relatively small suspension half-life and are largely filtered out by the nose and upper airway.Researchers define a diameter between2.5and10μm(PM2.5–10)as “coarse,”less than2.5μm as“fine,”and less than0.1μm as“ultrafine”particles.When interpreting PM research,it is important to appreciate that PM10contains ultrafine(PM0.1), fine(PM0.1–2.5),and coarse(PM2.5–10)fractions.In a mixed environmental sample,the total number and total surface area of these particles increases exponentially as the diam-eter of the particle decreases.However,the total particulate mass of a substance generally decreases exponentially with decreasing particle diameter.For example,in a sample of PM10,the numerical majority of particles would be ultra-fine,but these particles would make up a negligible portion of the sample's total particulate mass(Fig.1).Studies show an increase in morbidity and mortality related to PM exposure.While the increased daily risks from PM exposure are modest for any individual,the costs of the worldwide healthcare burden are staggering when applied to populations.The World Health Organization estimates that PM2.5concentration contributes to approximately800,000 premature deaths per year,ranking it the13th leading cause of mortality worldwide[6].This paper provides a review of the effect of ambient airborne PM on human morbidity and mortality.We review the current understanding of the mechanisms that underlie the observed clinical findings.Emphasis is placed primarily on research concerning the cardiovascular,respiratory,and cere-brovascular systems.This review concludes with public health recommendations based on a summary of the reported literature's findings.MethodsThe authors conducted a scientific review of all available literature published over the last30years.Our primary objective was to determine the association or lack of asso-ciation between PM and human health.Our secondary ob-jective was to summarize the proposed mechanisms for any purported associations based on existing human,animal, and in vitro studies.We initiated a PubMed database search using the MESH terms“PM,”“particulate matter,”“air pollution,”“ultrafine particles,”“fine particles,”“coarse particles,”“PM10,”“PM2.5,”and“PM0.1.”Articles were selected and agreed upon by the authors based on relevance and impact.Effort was made to provide both positive and negative studies where appropriate.Emphasis was placed on well-conducted trials and epidemiological investigations. Studies were only excluded for redundancy.After analysis of the available data,this paper concludes with individual and public health recommendations based on the existing scientificevidence.Fig.1A hypothetical mixed particle distributionPM and Cardiovascular Health EffectsSeveral large studies suggest that PM exerts significant effects on the cardiovascular system[7–9].Research on this topic has focused on both the long-term effects of chronic PM exposure and the acute effects of increases in ambient PM on cardio-vascular mortality.In a previous analysis[10],it was shown that for any increase in mortality caused by PM,two thirds of the effect was accounted for by the cardiovascular diseases. Cardiovascular MechanismsAnimal studies demonstrate a link between chronic PM expo-sure and the development of atherosclerosis via systemic inflam-mation[11,12].Human studies show that the effects appear to be mediated by the inflammatory cytokines IL-6,TNF-ά,and C-reactive protein(CRP).Increases in both IL-6[13]and CRP[14] have been associated with the development of acute myocardial infarction.Ruckerl et al.[15]described transient IL-6and TNF-άelevations in diabetic patients for2days following PM10 exposure.In a prospective cohort study of German patients, Hoffman et al.[16]associated exposure to PM2.5with eleva-tions in CRP.Other researchers demonstrated similar increases in CRP from PM10exposure from both combustion[17]and organic matter[18].In contrast,some studies have found only a weak or absent link between PM and markers of inflammation [19–22].Discrepancies among studies appear related to differ-ences in composition of PM,variable exposure to anti-inflammatory medications,and differences in obtaining PM exposure data[10].Acute exposure to PM causes changes in coagulation and platelet activation providing a more proximal link between PM and coronary artery disease.Many experts consider fibrinogen to be an important risk factor for cardiovascular disease[10].Ruckerl et al.[15]associated a5-day cumulative exposure to PM10with increased fibrinogen levels in survi-vors of myocardial infarction.Other pro-coagulant factors, such as plasminogen activator fibrinogen inhibitor-1(PAI-1),were also associated with PM elevations[17].Intratracheal instillation of diesel exhaust particles led to increased platelet activation in hamsters and rapid thrombosis formation[23]. Further hamster studies also suggested that small particles translocate into the blood stream and exert prothrombotic effects[24].Schicker et al.[18]showed that transient increases in PM10exposure caused during hay-stacking increased platelet aggregation within2h of the activity.This activity also increased V on Willebrand factor and Factor VIII, markers of vascular endothelial activation.Long-Term EffectsThe“Harvard Six Cities study[7],”a cohort study published in1993,followed8,111patients for16–18years and showed a29%(95%CI,8–47%)increase in the adjusted mortality rate for the most polluted of the cities compared to the least polluted.Particulate air pollution was positively associated with death from lung cancer and cardiopulmo-nary disease(Table1).Pope et al.[8]followed this in1995with another prospec-tive cohort study of552,000patients in151metropolitan areas using the American Cancer Society's Cancer Prevention2 database(ACS CPS2).These data showed a17%(95%CI, 9–26%)increase in all-cause mortality and a31%(95%CI,17–46%)increase in cardiopulmonary mortality when comparing the most and least polluted cities.In2002[25]and2004[26], Pope et al.re-reviewed the expanding ACS CPS2database, now with1.2million participants,and extended the follow up. Their research demonstrated an average increase in cardiopul-monary mortality of9%(95%CI,3–16%)for each10-μg/m3 increase in PM2.5.Subsequently,they determined that a10-μg/ m3increase in PM increased ischemic cardiovascular disease mortality by18%(95%CI,14–23%)and mortality from arrhythmia,congestive heart failure,and cardiac arrest by 13%(95%CI,5–21%).In2007,the Women's Health Initiative Study[27]followed a cohort of over65,000postmenopausal women with no previousTable1Long-term effects of PM on the cardiovascular systemPM particulate matter,ΔPM in-crease in ambient PM,BS black smoke Author Year PMΔPM(inμg/m3)Outcome measure Effect(95%CI)Dockery et al.[17]1993PM1018.6All-cause mortality26%(8–47) Pope et al.[18]1995PM1024.5All-cause mortality17%(9–26)PM1024.5Cardiopulmonary mortality31%(17–46) Hoek et al.[28]2002BS10.3Cardiopulmonary mortality71%(10–167) Pope et al.[25]2002PM2.510Cardiopulmonary mortality9%(3–16) Pope et al.[26]2004PM2.510Ischemic CVD mortality18%(14–23)PM2.510CHF,arrhythmia,CP arrest13%(5–21) Miller et al.[27]2007PM2.510Cardiovascular event24%(9–41)PM2.510Cardiovascular mortality76%(25–147) Toren et al.[29]2007PM Not measured Cardiovascular mortality12%(7–19)heart disease over approximately6years.The investigators revealed that long-term PM exposure in this population resulted in a24%(95%CI,9–41%)increase in cardiovascular events and an astonishing76%(95%CI,25–147%)increase in cardio-vascular mortality per10-μg/m3increase in PM2.5.While these results had fairly wide confidence intervals,these data suggest that this cohort of patients may be particularly susceptible to ambient PM exposure.The findings of cardiovascular effects from PM exposure are not unique to the USA.In the Netherlands,long-term exposure to traffic-related air pollution increased cardiopul-monary mortality by71%(95%CI,10–167%)[28].A2007 cohort study[29]of250,000Swedish construction workers from1972to2002found that workers with occupational PM exposure had a12%(95%CI,7–19%)increase in ischemic cardiovascular disease mortality.While increases in PM have been consistently shown to increase cardiovascular morbidity and mortality,the effects of PM reduction have also been studied.In the72months fol-lowing the ban of bituminous coal sales in Ireland in1990, black smoke concentration decreased by35.6μg/m3over this time,and standardized respiratory and cardiovascular mortal-ity decreased by15.5%(95%CI,12–19%)and10.3%(95% CI,8–13%),respectively[30].An8-year extension of the Harvard Six Cities data studied the population subset that moved from areas of higher to lower PM concentration[31], finding that a10-μg/m3decrease in PM2.5resulted in a27% (95%CI,5–43%)decrease in overall mortality.Short-Term EffectsA2001review[32]of12prior studies concluded that a10-μg/ m3increase in PM10increased hospital admissions for conges-tive heart failure and ischemic heart disease by0.8%(95%CI,0.5–1.2%)and0.7%(95%CI,0.4–1.0%),respectively.Simi-larly,a2006review[33]showed a0.44%(95%CI,0.02–0.86%)and1.28%(95%CI,0.78–1.78%)increase in admis-sions for ischemic heart disease and heart failure for a10-μg/m3 increase in PM2.5,respectively.In a smaller trial,Pope et al.[34]used a case-crossover of12,000patients in Utah to show that a10-μg/m3increase in PM2.5led to a4.5%(95%CI,1.1–8.0%)increase in acute ischemic coronary events.In an anal-ysis of PM concentrations from20major cities in the USA using the National Morbidity Mortality Air Pollution Study (NMMAPS)data,Samet et al.[9]showed a10-μg/m3increase in PM10caused an increase in all-cause and cardiopulmonary mortality by0.5%(95%CI,0.1–0.9%)and0.7%(95%CI,0.2–1.2%),respectively(Table2).Similar results have been found in Japan[35],Australia, and New Zealand[36].In2008,Samoli et al.[37]re-analyzed the data of the APHEA2,NMMAPS,and several Canadian studies in order to assess the coherence of findings using the same methods for all three sets of data.They were able to show an increase in daily all-cause mortality for Canadian, European,and US cities.Interestingly,the short-term mortal-ity resulting from acute increases in PM are not limited to the critically ill or dying.In fact,much of the mortality occurred among active individuals with one or more risk factors.PM and Respiratory Health EffectsWhile much of the interest in PM has focused on the cardiovascular system[7,8],many studies evaluated the association between PM exposure and respiratory illness. Researchers have evaluated endpoints including respiratory symptoms,medication use,lung function,health-care utili-zation,and mortality.Table2Short-term effects of PM on the cardiovascular systemPM particulate matter,ΔPM in-crease in ambient PM,TSP total suspended particles,IHD ische-mic heart disease,CHF conges-tive heart failure,AMI acute myocardial infarction Author Year PMΔPM(inμg/m3)Outcome measure EffectMorris[32]2001PM1010Hospital admission,IHD0.7%(95%CI,0.4–1.0)PM1010Hospital admission,CHF0.8%(95%CI,0.5–1.2) Domicini etal.[33]2006PM2.510Hospital admission,IHD0.44%(95%CI,0.02–0.86) PM2.510Hospital admission,CHF 1.28%(95%CI,0.78–1.78) Barnett et al.[36]2006PM2.510Hospital admission,IHD 1.6%(95%CI,0.7–2.4)PM2.510Hospital admission,CHF 3.6%(95%CI,1.8–5.4)PM2.510Hospital admission,AMI 2.7%(95%CI,1.3–4.2) Pope et al.[34]2006PM2.510Ischemic cardiac event 4.5%(95%CI,1.1–8.0) Samet et al.[9]2000PM1010All-cause mortality0.5%(95%CI,0.1–0.9)PM1010Cardiopulmonarymortality0.7%(95%CI,0.2–1.2) Omori et al.[35]2003TSP20All-cause mortality 1.0%(95%CI,0.8–1.3)TSP20Cardiopulmonarymortality1.1%(95%CI,0.7–1.5)Respiratory MechanismsPM triggers pulmonary oxidative stress and inflammation. Human airway epithelial cells exposed to PM express in-flammatory cytokines[38,39].Alveolar macrophages ex-hibit respiratory burst activity,producing reactive oxygen species,nitrogen species,and release TNF-άand IL-1after exposure[40].In addition to oxidative stress generated from activation of inflammatory cells,reactive oxygen species may be directly generated from the surface of particles [41].These responses can be potent and were shown to cause measurable pulmonary damage after only a single exposure in mice[42].This oxidative damage is associated with the primary development of asthma and chronic ob-structive pulmonary disease(COPD).Long-term exposure to PM results in airway remodeling and chronic inflamma-tion[43].PM may also contribute to asthma development by enhancing atopy and IgE responses[44,45].Several controlled human experiments have demonstrated adverse affects on the pulmonary system.PM exposure has been shown to increase airway responsiveness to methacholine [46],increase neutrophil numbers in bronchial lavage[47], decrease CO diffusion capacity,and decrease maximum mid-expiratory flow[48].Respiratory Symptoms and Medication UsageAs part of the Children's Health Study,McConnell et al.[49] found that asthmatic children had a40%(95%CI,10–80%) increased risk of bronchitic symptoms for a19-μg/m3increase in PM10.Similarly,a10-μg/m3increase in PM10led to a12% (95%CI,4–22%)increase in severe asthma symptoms in Seattle children[50].A study of inner-city asthmatic children revealed an association between PM2.5increases and missed school days for asthma[51].A study of adult Parisians[52] showed a41%(95%CI,16–71%)increase in acute asthma exacerbations per10-μg/m3increase in PM10.Interestingly, nearly all PM levels in these studies were below levels set out in the NAAQS.Respiratory medication use also increased in times of peak PM e of rescue bronchodilators increased as ambient PM2.5rose in Denver[53]and the Northeast USA [54].A review of80,000Alaskan Medicaid enrollees found prescription rates for bronchodilators increased by18.1%and 28.8%when PM10exceeded34and61μg/m3,respectively [55].Together,these data suggest that increases in ambient PM worsen asthma symptoms.PM and Pulmonary FunctionSeveral recent studies suggest that PM levels may affect lung function and lung development.The Children's Health Study [56]followed1,759patients over8years,finding that children who lived in communities with the highest PM concentrations were five times more likely to have low FEV1than those in communities with the lowest PM concentrations.Moreover, children that moved from areas of higher to lower PM10con-centration had increased growth in lung function,and those that moved from areas of lower to higher PM10concentration had decreased growth in lung function[57].Even children with better lung function were susceptible to new onset asthma when exposed to higher levels of PM2.5[58].Lower lung function has also been shown for children with cystic fibrosis exposed to higher levels of PM10and PM2.5[59].Similar inverse correlations between PM exposure and individual PEFR and FEV1measurements have been repro-duced internationally[60].In the developing world,where indoor biomass burning can lead to PM levels exceeding 200μg/m3,researchers demonstrated that chronic exposure in children can lead to adult COPD,increased rates of lung infection,and impaired lung function[61].In adults,effects of PM on lung function have been found primarily in susceptible populations.Investigators showed that asthmatic Londoners taking walks in areas of high PM had significantly higher reduction in FEV1,FVC,and increases in sputum biomarkers of inflammation[62].In elderly patients,PM10and PM2.5increases were associated with decreases in PEFR[63].In COPD patients,decrements in lung function were associated with increases in PM2.5 concentration[64].Downs et al.[65]demonstrated that declines in PM10concentration may actually lead to an atten-uated decline in lung function in adult patients.However, research on healthy adults has not as consistently shown an association between PM and respiratory compromise[66].PM and Respiratory-Related Healthcare UtilizationIn a large case–control study[67],10μg/m3increases in PM2.5were associated with a9%(95%CI,4–14%)increase in bronchiolitis hospitalizations for rge pediatric studies demonstrate increased asthma ED visits for increases in PM[68]and that PM10increases of6.5μg/m3are associ-ated with a15%(95%CI,2–30%)increase in respiratory-related hospital admissions[69](Table3).For adults,several large studies have demonstrated an association between respiratory hospitalization and ambient PM10[70]and PM2.5[71]concentrations.This includes admissions for asthma,COPD,and pneumonia.The effects appear to be stronger for elderly patients with even short-term exposures[72].A study[73]of12million Medicare enrollees in108counties demonstrated significant increases in respiratory hospitalizations for increases in PM2.5in the Eastern USA.Because the same effects were not consistent-ly observed in the Western USA,the authors suggested that morbidity may be related to the specific chemical constitu-ents of PM which differs across the country.Several recentlarge studies have provided further evidence that the strength of PM effect may depend on the composition [74].Investigations in European cities[75],Asian cities [76],and Oceania cities[77]have demonstrated a consistent and small though significant association between PM con-centrations and emergency visits for respiratory diseases.PM and Respiratory MortalityThe Six Cities study[7],20cities study[9],and ACS CPS2 [8]cohort revealed an association between PM exposure and cardiopulmonary mortality.These studies did not,however, separate the impact on respiratory mortality versus cardiovas-cular mortality.A follow-up investigation using data from the 20Cities Study revealed a0.87%(95%CI,0.38–1.36%) increased respiratory mortality for short-term increases in PM10by10μg/m3[78].This was subsequently expanded intoa larger cohort of112US cities,where researchers found a1.68%(95%CI,1.04–2.33%)increase in respiratory mortality for every10-μg/m3increase in PM2.5[79].A study of Cal-ifornia counties similarly revealed an increased respiratory mortality with increases in PM10[80].These results have been reproduced in countries around the world.A Norwegian study[81]demonstrated a17% (95%CI,9–25%)increase in mortality risk from COPD for every quartile increase in PM2.5.In a study of275,000 adults in ten Italian cities[82],short-term PM10increases led to a2.29%(95%CI,1.03–3.58%)increase in respiratory mortality.Similar results for increased respiratory mortality have been found in Asian cities where researchers have demonstrated excess respiratory mortality risk for increases in PM10[83].Nearly identical effect sizes for respiratory mortality were found in the APHEA2trial which studied this relationship across29European cities[84].One study even demonstrated an association between PM10and respi-ratory mortality in children under age five[85](Table4). PM and Cerebrovascular Health EffectsIschemic cerebrovascular and cardiovascular disease share many risk factors,features,and pathophysiological mecha-nisms.As an example,CRP,similar to cardiovascular dis-ease,has also been implicated in the genesis of stroke[86].Table4The effects of PM on respiratory mortalityPM particulate matter,ΔPM in-crease in ambient PM Author Year PMΔPM(inμg/m3)Outcome measure Effect(95%CI)Zeka et al.[78]2005PM1010Respiratory mortality0.87%(0.38–1.36) Zanobetti et al.[79]2009PM2.510Respiratory mortality 1.68%(1.04–2.33) Wong et al.[83]2008PM1010Respiratory mortality0.62%(0.22–1.02) Analitis et al.[84]2006PM1010Respiratory mortality0.58%(0.21–0.95) Hales et al.[91]2010PM1010Respiratory mortality 1.3%(0.5–2.1) Pope et al.[25]2002PM2.510Lung cancer mortality8%(1–16)Ostro et al.[80]2006PM2.510Respiratory mortality 2.2%(0.6–3.9)Table3The effects of PM on respiratory admissionsPM particulate matter,ΔPM increase in ambient PM Author Year PMΔPM(inμg/m3)Outcome measure Effect(95%CI)Karr et al.[67]2006PM2.510Infant bronchiolitisadmissions9%(4–14)Lin et al.[68]2005PM10–2.5 6.5Pediatric respiratoryadmissions17%(6–29)Samoli et al.[92]2011PM1010Pediatric asthma admissions 2.54%(0.06–5.08) Peng et al.[93]2008PM10–2.510Respiratory admissions0.33%(−0.21–0.86) Zanobetti et al.[70]2009PM2.510Respiratory admissions 2.07%(1.2–2.95)PM2.517Pneumonia admissions 6.5%(1.1–11.4) Medina-Ramonet al.[71]2006PM1010COPD admissions 1.47%(0.93–2.01)PM1010Pneumonia admissions0.84%(0.5–1.19) Dominici et al.[33]2006PM2.510COPD admissions 1.61%(0.56–2.66)McGowan et al.[77]2001PM1014.8Respiratory admissions 3.37%(2.34–4.40)Ostro et al.[94]2009PM2.514.6Pediatric respiratoryadmissions4.1%(1.8–6.4)However,the evidence linking PM and stroke is more sporadic and the mechanisms less well understood.Dominici et al.[33]reviewed an air quality data for204 US urban counties and showed that a10-μg/m3increase in ambient PM2.5increased the risk of hospitalization for ce-rebrovascular events by0.8%(95%CI,0.3–1.3%).A sep-arate review[87]of Medicare patients found an increase of 1.03%(95%CI,0.04–2.04%)for hospital admission for ischemic stroke for each10-μg/m3increase in PM10.Still other investigators found a previous day PM2.5increase of 5.2μg/m3led to a3%(95%CI,0–7%)increase in risk of TIA and ischemic stroke.In contrast,a recent large prospective multi-center stroke registry found no increase in the general popula-tion for ischemic stroke from exposure to PM2.5.There was,however,an11%(95%CI,1–22%)increase in stroke risk in exposed patients with diabetes[88].A large case-crossover study found an association between other components of air pollution(NO2and CO)and cerebrovascular disease,but no correlation was noted with changing PM levels[89].Similarly,a large registry of first-ever strokes found no association with PM10for ischemic or hemorrhagic stroke[90].There are several reasons why studies of PM and cere-brovascular disease have produced conflicting results.Some studies do not completely adjust for all confounding varia-bles.There is further heterogeneity due to differences in the definition of cerebrovascular disease,or whether pollution is measured on the day of admission or symptom onset[88]. Further,it is possible that exposure to PM may not contrib-ute to an overall increase in cerebrovascular disease,but only trigger events in vulnerable populations.Recommendations and ConclusionsIn evaluating the literature,there appears to be a small,but consistent and significant,effect of PM on human health. Overall,the small individual effects result in a large global public health burden.Notably,the effects are most pronounced for cardiovascular disease.Several studies have demonstrated an increase in cardiovascular mortality and hospitalizations. There are similar effects,of smaller amplitude,in respiratory disease.More study is needed to clarify the relationship be-tween PM and cerebrovascular disease.There are limitations to much of the available PM research. Most studies do not use individual exposure data.Rather,air monitors in population centers are used as surrogates for individual exposure.Even after adjusting these data for time spent in traffic,exposure to second-hand smoke,etc.,esti-mates may not be accurate.Despite these limitations,different types of studies conducted in different locations find similar results.A dose–response relationship between PM exposure and adverse effects has been identified,and improvement in health endpoints is observed when the PM exposures are reduced.Overall,the available evidence suggests a causal association between long-and short-term PM exposure and cardiovascular and respiratory morbidity and mortality.Further research is still needed to fully understand how PM affects human health.While studies show increased PM con-centration has adverse health affects,the actual composition of particulates that is harmful has not yet been elucidated.Further studies are also needed to clarify the time course of PM-induced effects.In limited studies,some effects seem to ap-pear within hours,while other reach their zenith within several days peak PM exposure.The data on this“lag time”effect canTable5Air quality index and recommendationsEPA-456/F-09-002Air quality index:a guide to air quality and your health.EPA, August2009AQI air quality indexa People with heart or lung dis-ease,children,or older adults AQI level AQIvaluePM2.5PM10Actions to protect yourhealth from particle pollutionGood0–500–150–50NoneModerate51–10016–3551–154Unusually sensitive peopleshould consider reducingprolonged or heavy exertion Unhealthy forsensitive groups101–15036–65155–254Susceptible groups a should reduceprolonged or heavy exertionEveryone else should limit prolongedor heavy exertionUnhealthy forsensitive groups151–20066–150255–354Susceptible groups a should avoidall physical activity outdoorsEveryone else should avoid prolongedor heavy exertionVery unhealthy201–300>150>354Susceptible groups a should remainindoors and keep activity levels lowEveryone else should avoid all physicalactivity outdoors。